Role of autophagy in aneurysm and dissection of the ascending aorta

2020 ◽  
Vol 16 (5) ◽  
pp. 517-526
Author(s):  
Mario Lusini ◽  
Antonio Nenna ◽  
Camilla Chello ◽  
Salvatore Matteo Greco ◽  
Ilaria Gagliardi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Shear Stress ◽  
Aortic Dissection ◽  
Vessel Wall ◽  
Ascending Aorta ◽  
Postoperative Treatment ◽  
Autophagic Flux ◽  
The Novel ◽  
Normal Vessel

Maintenance of physiologically balanced levels of autophagy is crucial for cellular homeostasis and in the normal vessel wall, balanced autophagy can be considered a cytoprotective mechanism that preserves endothelial function and prevents cardiovascular disease. Recent studies pointed out the importance of the modulation of the autophagic flux in the pathogenesis of aortic dissection and aneurysms of the ascending aorta. Notably, shear stress (and its receptor p62), IL-6, Rab7 and Atg5/IRE1α pathways of autophagy may be considered the novel super-selective therapeutic target for the preventive and postoperative treatment of aortic aneurysm and aortic dissection. This review intends to summarize current evidences in this field trying to enlighten new avenues for future researches.

scholarly journals Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

2018 ◽  
Vol 315 (5) ◽  
pp. H1477-H1485 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Atp Release ◽  
Vascular Endothelial ◽  
The Novel ◽  
Caveolin 1 ◽  
Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

scholarly journals Systemic Role for Vitamin D in the Treatment of Psoriasis and Metabolic Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Lisa Wenyang Fu ◽  
Ronald Vender
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Vitamin D ◽  
Inflammatory Diseases ◽  
Systemic Disease ◽  
The Novel ◽  
Oral Vitamin ◽  
Potential Use

The novel discovery of the systemic role of vitamin D in the modulation of the immune system especially the Type 1 helper T cell (Th1) pathway reveals its potential for treating Th1 inflammatory diseases. Psoriasis has been recently established to be a systemic disease centered on inflammation and involvement of cytokines of the Th1 pathway. There is an increased prevalence of metabolic syndrome in patients with psoriasis. Metabolic syndrome also involves a proinflammatory state. This paper proposes the idea of the potential use of oral vitamin D to treat psoriasis and metabolic syndrome concurrently. We propose there is merit in more clinical trials investigating the use of vitamin D to treat both psoriasis and metabolic syndrome through its anti-inflammatory effects. On application to psoriasis management and prognosis, the goal is to decrease the risk for cardiovascular disease and decrease disease morbidity and mortality.

Nitric oxide generation by endothelial cells exposed to shear stress in glass tubes perfused with red blood cell suspensions: role of aggregation

2008 ◽  
Vol 294 (5) ◽  
pp. H2098-H2105 ◽  
Author(s):  
Ozlem Yalcin ◽  
Pinar Ulker ◽  
Ugur Yavuzer ◽  
Herbert J. Meiselman ◽  
Oguz K. Baskurt
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Vessel Wall ◽  
Plasma Viscosity ◽  
Autologous Plasma ◽  
Rbc Aggregation

Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm2. RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.

Role of hemodynamic shear stress in cardiovascular disease

2011 ◽  
Vol 214 (2) ◽  
pp. 249-256 ◽  
Author(s):  
Emanuele Cecchi ◽  
Cristina Giglioli ◽  
Serafina Valente ◽  
Chiara Lazzeri ◽  
Gian Franco Gensini ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Shear Stress ◽  
Hemodynamic Shear Stress

The role of echocardiography

2021 ◽  
pp. 747-755
Author(s):  
Arturo Evangelista ◽  
Gisela Teixidó-Turà
Keyword(s):  
Aortic Dissection ◽  
Imaging Techniques ◽  
Transoesophageal Echocardiography ◽  
Left Ventricular ◽  
Ascending Aorta ◽  
Emergency Setting ◽  
Aortic Diseases ◽  
Echocardiographic Examination

Echocardiography plays an important role in the diagnosis and follow-up of aortic diseases. Evaluation of the aorta is a routine part of the echocardiographic examination. Transthoracic echocardiography (TTE) is an excellent modality for imaging the aortic proximal ascending aorta, which is important in the diagnosis and follow-up of aorta aneurysms. Transoesophageal echocardiography (TEE) overcomes the limitations of TTE in thoracic aorta assessment. Although TEE is the technique of choice in the diagnosis of aortic dissection, TTE may be used as the initial modality in the emergency setting. Intimal flap in proximal ascending aorta, pericardial effusion/tamponade, and left ventricular function can be easily visualized by TTE. However, a negative TTE does not rule out aortic dissection and other imaging techniques must be considered. TEE should define entry tear size and location, mechanisms and severity of aortic regurgitation, and true lumen compression. TEE is essential in selecting and monitoring surgical and endovascular treatment and in detecting possible complications.

scholarly journals Rôle of contrast media viscosity in altering vessel wall shear stress and relation to the risk of contrast extravasations

2016 ◽  
Vol 38 (12) ◽  
pp. 1426-1433 ◽  
Author(s):  
Sophia Sakellariou ◽  
Wenguang Li ◽  
Manosh C Paul ◽  
Giles Roditi
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Contrast Media ◽  
Vessel Wall ◽  
Wall Shear

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

2020 ◽  
Vol 134 (17) ◽  
pp. 2399-2418
Author(s):  
Yoshito Yamashiro ◽  
Hiromi Yanagisawa
Keyword(s):  
Shear Stress ◽  
Blood Vessels ◽  
Vessel Wall ◽  
Vascular Diseases ◽  
Cell Interactions ◽  
Aortic Aneurysms ◽  
Cyclic Stretch ◽  
Mechanical Stimuli ◽  
Vascular Homeostasis ◽  
Matrix Cell

Abstract Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

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